背景:商业妥布霉素眼用溶液经常用于经验治疗马的眼部疾病,尽管主要用于人类。已经注意到,妥布霉素MIC90浓度(微生物生长的90%的最小抑制浓度)在局部施用后迅速下降。假设用驴眼泪的pH值调节经验使用的妥布霉素眼用溶液-为人类使用制备-的pH值。可以增加药物的生物利用度,并随后改善其对房水的渗透。因此,这项研究旨在评估根据经验使用的妥布霉素眼用溶液的pH调节对驴(Equusasinus)的眼泪和房水中MIC90浓度的影响。该研究对6只(n=6)临床健康的驴进行。在每一头驴中,随机选择一只眼睛接受210μg妥布霉素的商业妥布霉素(CT),并用作阳性对照(C组,n=6)。另一只眼(治疗眼)接受210µg改良妥布霉素眼用溶液(MT)(T组,n=6)。收集泪液和房水样本5-,10-,15-,30-min,1-,2-,4-,和6小时后滴注。
结果:在8.26的pH下修改实验使用的商业妥布霉素眼用溶液在驴中的pH提高了药物的生物利用度。从马眼中分离出的最危险细菌的MIC90,例如铜绿假单胞菌(MIC90=128µg/ml)和金黄色葡萄球菌(MIC90=256µg/ml)被早期(滴注后5分钟)和更长的时间用改良的妥布霉素溶液覆盖驴眼泪(239-342分钟)和房水(238-330分钟)。
结论:调节市售妥布霉素眼用溶液的pH,兽医根据经验在pH值为8.26时治疗驴的眼科感染,与驴的眼泪pH值等渗,导致泪液和房水中的妥布霉素浓度更高,持续时间更长。
BACKGROUND: Commercial tobramycin ophthalmic solution is frequently used empirically to treat ocular disorders in equines, despite being primarily formulated for use in humans. It has been noted that tobramycin MIC90 concentration (minimal inhibitory concentration to 90% of microbial growth) rapidly declined following topical administration. It is hypothesized that adjustment of the pH of the empirically used tobramycin ophthalmic solution -prepared for human use- with the pH of the tears of donkeys, could increase the bioavailability of the drug and subsequently improve its penetration to the aqueous humor. Therefore, this study aimed to evaluate the impact of pH adjustment of the empirically used tobramycin ophthalmic solution on MIC90 concentration in tears and aqueous humor of donkeys (Equus asinus). The study was conducted on six (n = 6) clinically healthy donkeys. In each donkey, one eye was randomly selected to receive 210 µg tobramycin of the commercial tobramycin (CT) and used as a positive control (C group, n = 6). The other eye (treated eye) received 210 µg of the modified tobramycin ophthalmic solution (MT) (T group, n = 6). Tears and aqueous humor samples were collected 5-, 10-, 15-, 30- min, and 1-, 2-, 4-, and 6 h post-instillation.
RESULTS: Modifying the pH of the empirically used commercial tobramycin ophthalmic solution in donkeys at a pH of 8.26 enhanced the drug\'s bioavailability. The MIC90 of the most hazardous bacteria isolated from equines\'
eyes such as Pseudomonas aeruginosa (MIC90 = 128 µg/ml) and Staphylococcus aureus (MIC90 = 256 µg/ml) was covered early (5 min post-instillation) and over a longer period in donkey tears (239-342 min) and aqueous humor (238-330 min) with the modified tobramycin solution.
CONCLUSIONS: Adjustment of the pH of the commercial tobramycin ophthalmic solution, empirically used by veterinarians to treat donkeys\' ophthalmic infections at a pH of 8.26, isotonic with the donkeys\' tears pH, resulting in higher concentrations of tobramycin in tears and aqueous humor for a longer time.